OBJECTIVES: The objectives of this project are to determine the site, location, and mechanisms of action of a series of peptides extractable from brain which exhibit opioid pharmacological actions. SUMMARY: At least two different opioid peptide-secreting cell systems occur within the brain, two more in pituitary, and others may be located within the peripheral autonomic nervous system and gut. Beta-endorphin, the most potent electrophysiologically and behaviorally, is much more restricted in distribution within the brain than are the enkephalins. Pituitary endorphin is secreted into the blood stream but no peripheral receptors have been identified. The prohormone for pituitary endorphin may include ACTH but that for brain has not yet been so characterized; brain endorphin is not likely to be a precursor peptide for enkephalins.